PB2383: MICROSATELLITE INSTABILITY AND 9P24.1 ALTERATIONS IN HODGKIN LYMPHOMA
Authors: Ekaterina Tregubova, Maria Sarpova, Elena Nazarova, Dmitry Diakonov
Journal: HemaSphere (2023)

Topic: 20. Lymphoma Biology & Translational Research Background: With the introduction into clinical practice of immune checkpoint inhibitors, in particular programmed cell death-ligand 1 (PD-L1), progress has been made in the treatment of refractory malignancies. Overexpression of PD-L1 and high microsatellite instability (MSI-H) are well-known predictive biomarkers. They predict the effect of checkpoint inhibitors in various solid tumors. Malignant cells at classical Hodgkin lymphoma (cHL) are also characterized by the expression of PD-L1, the level of which depends on the CD274 gene aberrations in the 9p24.1 loci. There are also data on the association of the PD-1 ligand level with the microsatellite instability, but due to the small number of tumor cells, the nature and prognostic significance of these alterations in cHL remain unclear. Aims: To determine the occurrence of microsatellite instability and chromosomal alterations of 9p24.1 in classical Hodgkin lymphoma. Methods: 49 samples of tumor tissue from patients with newly diagnosed cHL were analyzed. Among them, the disease progression was found in 9 (18,4%) cases. Standard protocols of therapy (ABVD, BEACOPP) were used as the first line in all patients. The MSI was evaluated by polymerase chain reaction using a kit “CorDIS MSI” (“Gordiz”, Russia), followed by fragment analysis of amplification products by capillary electrophoresis on a genetic analyzer ABI 3500xL (“Thermo Fisher Scientific”, USA). Aberration in 9p24.1 were assessed by in situ fluorescent hybridization using CD274/PDCD1L/9qhet FISH probe (CytoCell, UK) on an Axio Scope.A1 microscope (Zeiss, Germany). Statistical analysis of the results was carried out using nonparametric methods. The differences were considered statistically significant at p<0.05. Results: The occurrence of microsatellite instability in cHL was 10,2% (5/49). In all cases, the status of low MSI is assigned. Cases without of microsatellite repeats instability were considered stable (MSS). When analyzing of 9p24.1 alterations an increase in the copies gain was detected in 30 (61,2%) patients, amplification 12 chromosome (24,5%), normal/polysomy of chromosome 9 in 7 (14,3%) cases. Comparison of the detected 9p24.1 aberrations with the effect of therapy revealed statistically significant differences. Thus, the frequency of 9p24.1 gain was higher in patients who achieved a complete response (57,1%; 28/49; p=0,003), while normal/polysomy of chromosome 9 was more common in patients with a refractory disease (8,2%; 4/49; p=0,003). When comparing MSI status and 9p24.1 alterations, no statistically significant differences were found (p=0,097). Summary/Conclusion: Microsatellite instability was detected in 10,2% of newly diagnosed classical Hodgkin lymphoma cases. Among the chromosomal alterations 9p24.1, an increase samples with the gain and amplifications were more common. Taking into account the limited quantity of observations, further studies are planned to use MSI status and CD274 gene aberrations as additional prognostic biomarkers for the stratification patients on cHL unfavorable course groups. Keywords: Hodgkin’s lymphoma, Genomic instability